Health workers scramble to contain deadly rat-borne fever in Nigeria

By early January, it was clear something “really, really extraordinary” was going on in Nigeria, says Lorenzo Pomarico of the Alliance for International Medical Action (ALIMA). Cases of Lassa fever, a rare viral hemorrhagic disease, were skyrocketing across the country—more were recorded in the first 2 months of this year than in all of 2017. Unprepared for a disease that has no vaccines or drugs for treatment and kills 20% to 30% of those it sickens, eight health care workers were infected early on and three died. “Something was going very wrong with the outbreak,” Pomarico says.

Since then, the situation has only gotten worse. The rodent-borne disease is endemic in Nigeria and several other West African countries, fluctuating with the seasons and usually causing “a trickle” of cases a year, says Chikwe Ihekweazu, who heads the Nigeria Centre for Disease Control in Abuja. But as of 4 March, 353 cases had been confirmed across 18 states, with about 700 suspected cases, and 110 deaths. Ihekweazu says the record-setting figures are sure to be underestimates, because the disease is maddeningly hard to diagnose, and many cases go unreported.

Already, Nigeria’s fragile health care system is overwhelmed. The one dedicated Lassa fever ward in the country at Irrua Specialist Teaching Hospital has just 24 beds. Without access to proper training, health care workers continue to become infected—by now 16 cases have been reported, with one additional death.

As the government and its international partners scramble to set up isolation wards to stem the outbreak and deliver protective gear to health workers, researchers on three continents are racing to figure out what is driving the unprecedented outbreak. Is it simply better disease surveillance in the wake of Ebola, the similar but more deadly disease that began its rampage across West Africa in 2014? Has the virus changed in some way, are there more of the rats that carry it, or is a higher proportion of them infected? Or is another rodent capable of spreading the virus as well?

“There are lots of possible explanations,” says Stephan Günther of the Bernhard Nocht Institute of Tropical Medicine in Hamburg, Germany, whose team has worked in Nigeria for years. Considering how lethal Lassa fever is, shockingly little is known about it, he says. “We don’t know why people die. We don’t know about the pathophysiology of the disease. We don’t know the point of no return.”

That could be beginning to change. In 2016, the World Health Organization added Lassa fever to its list of priority pathogens of epidemic potential, calling for more research. And last week, the recently created Coalition for Epidemic Preparedness Innovations awarded its first grant for development of a Lassa fever vaccine to Themis Bioscience, a biotech in Vienna.

Lassa fever was discovered in 1969, when two missionary nurses died of a mysterious disease in the remote town of Lassa in Borno state in northeastern Nigeria. When a third nurse fell ill, she was evacuated to a hospital in New York City—along with a thermos full of blood and other samples from all three nurses bound for Yale University’s then-new Arbovirus Research Unit. There, a team led by Jordi Casals-Ariet isolated a novel virus from the samples. (He, too, almost died in the process, saved only by an infusion of antibody-rich plasma from the third nurse, who recovered.)

The cause is now known to be an arenavirus, one of a class of rodent-borne pathogens, and its natural reservoir is a multimammate rat, so-called for its rows of mammary glands, that is ubiquitous across West Africa. Cases peak in the dry season, when farmers burn the bushes in preparation for spring planting and rats scurry into houses in search of food. The rodents shed the virus in their urine and droppings, and people contract it by touching contaminated surfaces, inhaling viral particles, or eating contaminated food (including the rats themselves). Like Ebola, the virus can also be spread through contact with bodily fluids of an infected person. Such human-to-human transmission is thought to be rare for Lassa, unlike Ebola, except in hospital settings without proper infection control. But “the real rate of human-to-human transmission is unknown,” says Augustin Augier, secretary general of ALIMA in Paris, which has just launched a Lassa fever research program with the French medical institution INSERM.

No one knows the true incidence of the disease. “Most cases we have found are in places where there are hospitals and labs,” Günther says. “There is good reason to assume there are cases that are being overlooked.” And because the rat vector lives across a broad swath of the continent, the disease might also be endemic, but unrecognized, outside of West Africa, where it could be responsible for undiagnosed fevers.

Initial symptoms are easily mistaken for malaria or typhoid fever—body aches, sore throat, fever, nausea, diarrhea—before the disease progresses to organ failure, shock, and sometimes internal hemorrhaging. By the time doctors suspect Lassa fever, it’s often too late to save the patient. There is no rapid test; accurately diagnosing the disease requires a real-time polymerase chain reaction technique, but only three labs in Nigeria have that capability.

For now, the only treatment is a nonspecific antiviral drug, ribavirin. If it’s administered during the first 6 days of the illness, it seems to improve a patient’s prognosis, but “no one arrives before day 7,” Augier says. Nor is everyone convinced that ribavirin works in Lassa fever, as the only data come from the 1980s, Augier says.

Several potential drugs are on the horizon, in addition to the vaccine. Christian Happi at Redeemer’s University in Ede, Nigeria, and the Irrua Specialist Teaching Hospital is developing a rapid diagnostic test with colleagues at Tulane University in New Orleans, Louisiana; the Broad Institute in Cambridge, Massachusetts; and Zalgen, a company in Germantown, Maryland. Happi’s group and its international partners are also sequencing the virus “around the clock,” he says, and trying to figure out whether the genetic changes they have seen in the virus could have made it more transmissible or virulent.

For Happi, who diagnosed the first case of Ebola in Sierra Leone, the new attention to Lassa hasn’t come a moment too soon. “I used to scream and scream that Lassa is important, but no one listened,” he says. “I wrote so many grants” that were turned down. “Lassa fever is a disease of the poor … it is confined to a part of West Africa, and it is not viewed as a global threat.”

Meanwhile, the government and its partners are focusing on training health care workers and providing the basics needed for infection control, as well as educating a frightened public.

ALIMA’s Pomarico, who is leading ALIMA’s emergency response to the outbreak in the two hardest hit states of Edo and Ondo, hopes cases will subside with the rains and cooler weather, as they usually do. “But this year is different. “We are bracing for worst and preparing for the worst.”